This project concerns an investigation of the physico-chemical properties, kinetic capabilities, regulatory mechanisms and physiological roles of the cyclic nucleotide phosphodiesterases of mammalian tissues. These enzymes, which degrade cycle AMP and cyclic GMP, are of importance in the actions of a large number of hormones and also play a role in neurotransmission and the regulation of cell proliferation. Specific goals include: 1) The isolation, characterization, and subcellular localization of the insulin sensitive phosphodiesterase of liver, fat, and muscle tissues. 2) The analysis of differences between phosphodiesterases from normal and malignant tissues or models thereof. 3) The improvement of cytochemical methods for specifically localizing the different phosphodiesterases.